Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Comparing Different Treatments in Reducing Dissociative Seizure Occurrence (CODES)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02325544
Recruitment Status : Completed
First Posted : December 25, 2014
Last Update Posted : March 25, 2020
Sponsor:
Collaborators:
University of Edinburgh
University of Sheffield
University of Sussex
South London and Maudsley NHS Foundation Trust
Information provided by (Responsible Party):
King's College London

Brief Summary:

The study will test the hypothesis that Cognitive Behavioural Therapy plus Standardised Medical Care (SMC) will have greater clinical and cost effectiveness than SMC alone in treating adult patients with dissociative seizures which had not initially ceased after diagnosis.

About 12-20% of patients who attend neurology or specialist epilepsy clinics because of seizures do not in fact have epilepsy. Most of these people have what are referred to as dissociative (non-epileptic) seizures (DS). This means that they have episodes that resemble epileptic seizures but which have no medical reason for their occurrence and instead are due to psychological factors. In younger adults DS are about four times more common in women than men. A high percentage of these people will have other psychological or psychiatric problems and may have other medically unexplained symptoms. It is generally thought that people with DS will benefit from psychological treatments. However, studies on this have been small or have not compared the psychological therapy with the treatment people normally receive (standardised medical care). There is some evidence that cognitive behavioural therapy (CBT), which is a widely accepted talking therapy that focuses on the person's thoughts, emotions and behaviour, as well as considering the physical reactions and sensations that may occur in people's bodies, may lead to a reduction in how often people have DS. The investigators have previously developed a CBT package for people with DS. In a relatively small study by our group, published in 2010, people receiving CBT overall showed greater reduction in how often they had their DS. The investigators are now conducting a larger study, across several different hospitals, to obtain more definite results about the effectiveness of our CBT approach for DS.

The investigators aim to invite ~ 500 adult patients with DS (but without current active epilepsy), who have been given their diagnosis by a neurologist or specialist in epilepsy, to take part in their study. Up to 698 might be invited if insufficient patients are progressing to the RCT.

The investigators will collect initial information about these people and ask them to keep a record of how often they have their DS following diagnosis. Three months after the diagnosis, those who have agreed to take part in the study will be seen by a psychiatrist, who will undertake a psychiatric assessment and ask them about factors which may have led to the development of their DS. Patients who have continued to have DS in the previous 8 weeks and who meet other eligibility criteria and are willing to take part in the trial, will be randomly allocated to standardised medical care or CBT (plus standardised medical care) as further treatment for their seizures. These people will be asked to continue to complete seizure diaries and questionnaires, provide regular seizure frequency data following receipt of DS diagnosis and will need to be willing to attend weekly/fortnightly sessions if allocated to CBT. The investigators initially aim to randomise 298 people (149 to each study arm) although now allow for up to 356 to account for loss to follow-up.


Condition or disease Intervention/treatment Phase
Convulsion, Nonepileptic Conversion Disorder Dissociative Disorder Behavioral: Cognitive Behavioral Therapy Behavioral: Standardized Medical Care Not Applicable

Show Show detailed description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 368 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: COgnitive Behavioural Therapy Versus Standardised Medical Care for Adults With Dissociative Non-Epileptic Seizures: A Multicentre Randomised Controlled Trial (CODES)
Study Start Date : October 1, 2014
Actual Primary Completion Date : May 31, 2017
Actual Study Completion Date : June 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Seizures

Arm Intervention/treatment
Experimental: CBT+SMC
12 sessions of Cognitive Behavioural Therapy adapted for DS (plus one booster session) plus standardised medical care
Behavioral: Cognitive Behavioral Therapy

12 sessions of CBT (over 4-5 months) +1 booster session. Guided by a therapy manual and patient handouts; will involve setting homework tasks. Although treatment is manualised, it allows treatment to be formulation-based i.e. tailored to the person.

Standardised medical as described in other intervention.


Behavioral: Standardized Medical Care
Delivered by neurologists/ psychiatrists - both will be involved in discussing diagnosis. It will Include an information sheet about dissociative seizures and direction to self-help websites, general information provision about management of DS and support, consideration of psychiatric comorbidities / associated drug treatment and general review but no CBT techniques.
Other Name: Treatment as usual

Active Comparator: SMC
Standardised medical care provide by neurologist and/or psychiatrist
Behavioral: Standardized Medical Care
Delivered by neurologists/ psychiatrists - both will be involved in discussing diagnosis. It will Include an information sheet about dissociative seizures and direction to self-help websites, general information provision about management of DS and support, consideration of psychiatric comorbidities / associated drug treatment and general review but no CBT techniques.
Other Name: Treatment as usual




Primary Outcome Measures :
  1. Change in seizure frequency [ Time Frame: Outcome assessed at 12 month post randomisation, ]
    Monthly DS frequency


Secondary Outcome Measures :
  1. Change in informant rating [ Time Frame: Outcome assessed at 12 month post randomisation only ]
    A rating by an informant as to whether compared to study entry seizure frequency is worse the same better or whether they are seizure free; data collected 6 & 12 months post randomisation; 6 month measures are only collected for data modelling and to maintain participant involvement but the trial endpoint was measured at 12 months only;

  2. Change in self-rated seizure severity [ Time Frame: Outcome assessed at 12 month post randomisation only ]
    Two items from the Seizure Severity Scale (Cramer et al., 2002), asking how severe and bothersome DS were in the past month; data collected at baseline (recorded pre-randomisation) , 6 & 12 months post randomisation; 6 month measures are only collected for data modelling and to maintain patient involvement but the trial endpoint was measured at 12 months only.

  3. Seizure freedom [ Time Frame: Outcome assessed at 12 month post randomisation only ]
    Patient's self-reported longest period of seizure freedom between the 6- and 12-month follow-up and whether or not the patient is seizure free in the last 3 months of the trial; data collected 12 months post randomisation; the trial endpoint was measured at 12 months only.

  4. >50% reduction in seizure frequency [ Time Frame: Outcome assessed at 12 month post randomisation only ]
    The number of patients in each group who at the 6- and 12-month follow-up show >50% reduction in seizure frequency, compared to baseline (pre-randomisation); data collected at baseline and 6 & 12 months post randomisation; 6 month measures are only collected for data modelling and to maintain patient involvement but the trial endpoint was measured at 12 months only.

  5. Change in Quality of life (QoL) [ Time Frame: Outcome assessed at 12 month post randomisation only ]
    Health-related QoL using the SF-12v2 (Ware et al.,1996); data collected at baseline (recorded pre-randomisation) , 6 & 12 months post randomisation; 6 month measures are only collected for data modelling and to maintain patient involvement but the trial endpoint was measured at 12 months only.

  6. Change in QALYs [ Time Frame: Outcome assessed at 12 month post randomisation only ]
    We will use EQ-5D-5L (EuroQol group, 1990), a 5-domain, 5-level, multi-attribute scale collected at baseline (recorded pre-randomisation) , 6 & 12 months post randomisation; 6 month measures are only collected for data modelling and to maintain patient involvement but the trial endpoint was measured at 12 months only.

  7. Change in psychosocial functioning [ Time Frame: Outcome assessed at 12 month post randomisation only ]
    Work and Social Adjustment Scale (Mundt et al 2002) collected at baseline (recorded pre-randomisation) , 6 & 12 months post randomisation; 6 month measures are only collected for data modelling and to maintain patient involvement but the trial endpoint was measured at 12 months only.

  8. Change in psychiatric symptoms and psychological distress [ Time Frame: Outcome assessed at 12 month post randomisation only ]
    We will measure anxiety, depression and somatisation with the GAD7 (Spitzer et al., 2006), PHQ9 (Kroenke et al., 2001) and an extended PHQ15 (Kroenke et al., 2002; Sharpe et al., 2010), derived from the Patient Health Questionnaire which reflects DSM-IV diagnoses. We will also use a general measure of psychological distress, the CORE-10 (Connell & Barkham, 2007); this assesses self-reported global psychological distress; data collected at baseline (recorded pre-randomisation) , 6 & 12 months post randomisation; 6 month measures are only collected for data modelling and to maintain patient involvement but the trial endpoint was measured at 12 months only.

  9. Change in patients self-rated global outcome and satisfaction with treatment [ Time Frame: Outcome assessed at 12 month post randomisation only ]
    CGI Clinical Global Impression (Guy 1976) change score yields a self-rated global measure collected at 6 & 12 months post randomisation; 6 month measures are only collected for data modelling and to maintain patient involvement but the trial endpoint was measured at 12 months only.

  10. Clinician rating of change [ Time Frame: Outcome assessed at 12 month post randomisation only ]
    The CGI change scale will be rated by CBT therapists at the end of session 12 and by the SMC doctor at the 12-month follow-up.

  11. Change in health service use and informal care (self-report) [ Time Frame: Outcome assessed at 12 month post randomisation only ]
    Adapted Client Service Receipt Inventory (Beecham & Knapp, 2001); data collected at baseline (recorded pre-randomisation) , 6 & 12 months post randomisation; 6 month measures are collected for data modelling and to give a total health service use over the 12 months of the post-randomisation period and to maintain patient involvement but the trial endpoint was measured at 12 months only.

  12. Change in health service use [ Time Frame: Outcome assessed at 12 months post randomisation ]
    Linkage data sets from NHS Health and Social Care Information Centre (Hospital Episode Statistics) eDRIS (NHS National Services Scotland Information Services Division (ISD) and Wales (NHS Wales Informatics Service)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. The inclusion criteria applied at the initial recruitment stage will be as follows:

    • adults (≥18yrs) with DS that have continued to occur within the previous 8 weeks and have been confirmed by video EEG telemetry or, where not achievable, clinical consensus; patients who have chronic DS can be included if they have been seen by the relevant Study Neurologist who has reviewed their diagnosis and communicated this to them according to the Study protocol
    • ability to complete seizure diaries and questionnaires;
    • willingness to complete seizure diaries regularly and undergo psychiatric assessment 3 months after DS diagnosis;
    • no documented history of intellectual disabilities;
    • ability to give written informed consent.
  2. Inclusion criteria evaluated at the randomisation stage will be as follows:

    • adults (≥18yrs) with DS initially recruited at point of diagnosis;
    • willingness to continue to complete seizure diaries and questionnaires;
    • provision of regular seizure frequency data following receipt of DS diagnosis;
    • willingness to attend weekly/fortnightly sessions if randomised to CBT
    • both clinician and patient think that randomisation is acceptable
    • ability to give written informed consent.

Exclusion Criteria:

The exclusion criteria applied at the initial recruitment stage will be as follows:

  • having a diagnosis of current epileptic seizures as well as DS. Patients with both DS and ES have been included in small studies but there is no method for verifying that patients can accurately differentiate between epileptic seizures and DS;
  • inability to keep seizure records or complete questionnaires independently;
  • meeting DSM-IV criteria for current drug/alcohol dependence;
  • insufficient command of English to later undergo CBT without an interpreter or to complete questionnaires independently. Reasons for this include the need to self-rate secondary outcomes using scales not validated for non-English speaking populations, the considerable cost and uncertainty of being able reliably to engage sufficiently competent interpreters, and the need to demonstrate the delivery of therapy in terms of quality and manual adherence.
  • having previously undergone a CBT-based treatment for dissociative seizures at a trial participating centre
  • currently having CBT for another disorder, if this will not have ended by the time that the psychiatric assessment takes place.

Exclusion criteria evaluated at the randomisation stage will be as follows:

  • current epileptic seizures as well as DS, for reasons given above;
  • not having had any DS in the 8 weeks prior to the psychiatric assessment, 3 months post diagnosis;
  • having previously undergone a CBT-based treatment for dissociative seizures at a trial participating centre
  • currently having CBT for another disorder
  • active psychosis;
  • meeting DSM-IV criteria for current drug/alcohol dependence; this may exacerbate symptoms/alter psychiatric state and health service use and affect recording of seizures;
  • current benzodiazepine use exceeding the equivalent of 10mg diazepam/day;
  • the patient is thought to be at imminent risk of self harm, after (neuro)psychiatric assessment or structured psychiatric assessment by the Research Worker with the MINI, followed by consultation with the psychiatrist.
  • known diagnosis of Factitious Disorder

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02325544


Locations
Show Show 40 study locations
Sponsors and Collaborators
King's College London
University of Edinburgh
University of Sheffield
University of Sussex
South London and Maudsley NHS Foundation Trust
Investigators
Layout table for investigator information
Principal Investigator: Laura H Goldstein, PhD MPhil King's College London

Additional Information:
Publications:

Layout table for additonal information
Responsible Party: King's College London
ClinicalTrials.gov Identifier: NCT02325544    
Other Study ID Numbers: CSP 136836
First Posted: December 25, 2014    Key Record Dates
Last Update Posted: March 25, 2020
Last Verified: February 2016
Keywords provided by King's College London:
dissociative seizures,
psychogenic nonepileptic seizures
Additional relevant MeSH terms:
Layout table for MeSH terms
Seizures
Disease
Conversion Disorder
Hysteria
Dissociative Disorders
Pathologic Processes
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Somatoform Disorders
Mental Disorders
Histrionic Personality Disorder
Personality Disorders